Summary

Cytochrome P450 CYP2C9 gene variants have been associated with
hyperresponsiveness to small doses of warfarin and a higher bleeding
complication rate. The aim of this study was to investigate whether
CYP2C9 gene variants affect doses of drug prescribed to acquire the
target anticoagulation intensity and the occurence of bleeding complications.
In a cohort of 180 patients followed up at one specialized clinic
from the start of the anticoagulation with warfarin, we have investigated
whether CYP2C9 gene variants have affected doses of drug prescribed
to acquire the target anticoagulation intensity and the incidence
of bleeding complications.
The adjusted dose required of warfarin was higher among patients
with the CYP2C9*1 haplotype (5.6 mg) than those of patients carrying
the CYP2C9*2 (4.7 mg; p = 0.007, Scheffé’s test) or the CYP2C9*3
haplotype (4.0 mg; p <0.001, Scheffé’s test). The occurrence of bleeding
complications was more frequent among patients with the
CYP2C9*2 and/or the CYP2C9*3 haplotype than in carriers of the
CYP2C9*1 haplotype (OR: 2.57; 95% CI: 1.16-5.73). An interaction
between the presence of local bleeding sources and the CYP2C9*2
and/or the CYP2C9*3 haplotype was observed (p <0.001). Patients
with both local sites of potential bleeding and CYP2C9*2 and/or
the CYP2C9*3 haplotype had the higher estimated risk of bleeding
(OR: 12.81; 95% CI: 2.86-57.26).
CYP2C9 gene variants modulate the anticoagulant effect of the dose
of warfarin prescribed. The incidence of bleeding complications in
CYP2C9*2 and CYP2C9*3 carriers was significantly higher than that
in noncarriers and interacted with the presence of local bleeding
sources.